**5. Case reports targeting incretin analogs/GLP-1 receptor agonists**

The first incretin analogs exenatid [56], lixisenatid, liraglutide were used in persons with T2D to improve metabolic control and to reduce body mass - mostly when HbA1c exceeded 60 mmol/mol, BMI was over 35 kg/m2 and oral antidiabetic drugs failed. Their beneficial metabolic and cardiovascular effects were described recently in RCTs LEAD 1 – LEAD 6 [57–62] and LEADER. [63] We had the option to confirm their benefits in several persons.

#### **5.1 Effects of liraglutide on body mass and HbA1c**

Our case report from the year 2010 [64] demonstrates the benefits of treatment with liraglutide in a 57-year old obese woman (adequately treated for hypothyreosis) with recent evolution of metabolic syndrome. Four-month metformin (M) and liraglutide (L) therapy reduced both body mass index (**Figure 17**), and glycated haemoglobin (**Figure 18**) Even though the previous diabetes control was acceptable, the treatment with high doses oť metformin and sitagliptin (S) failed to reach sufficient reduction of body mass and HbA1c.

#### **Figure 17.**

*Lady, age 57. Therapy and evolution of BMI since the detection of T2D in 2006. M-metformin, S-sitagliptin, L-liraglutide (L-start 18.8.2010) [64].*

#### **Figure 18.**

*Lady, age 57. Therapy and evolution of HbA1c since the detection of T2D in 2006. M-metformin, S-sitagliptin, L-liraglutide (L-start 18.8.2010) [64].*

#### **Figure 19.**

*Man, age 57 y, T2D duration 13 y. Evolution of HbA1c with liraglutide and metformin before (2010–2012, blue) and after (2012–2015) bariatric surgery [65] (2015).*

**17**

**Figure 20.**

*Pathophysiologic Approach to Type 2 Diabetes Management: One Centre Experience 1980–2020*

Our second case report (2010–2016) [65] deals with a temporal positive influence of a 5-year liraglutide therapy on HbA1c (**Figure 19**), BMI and 10-point glyceamic profile in a man with 13-year history of uncontrolled T2D. After one year on liraglutide 1,2 mg/d + metformin 2000–3000 mg/d, the initial decrease of BMI and HbA1c was followed by their slow increase. Following bariatric surgery, the continuing liraglutide and metformin treatment resulted in near-normal HbA1c concentrations not exceeding 51 mmol/mol. The BMI decreased from

The purpose of this case report (2011) [66] is to demonstrate the effects of 5 month off label administration of L and metformin (M) in a 60y old woman with

excellent physical condition. Since 2005 her body mass increased by 10 kg. Recently diagnosed hypertension was successfully treated by metoprolol and losartan (BP 140/80 mmHg, HF 64/min). She was treated by simvastatin since 2008 (LDL cholesterol 3,4 mmol/l). Proinsulin, C-peptide, TSH. T3, T4 and routine laboratory parameters were found within normal limits. Results of SMPG using glucometer Linus, Agamatrix, USA were slightly abnormal. In August 2010 the therapy with L and M started. First evaluation was made in January 2011 (**Figures 20** and **21**). In 2012 – 2014, L 1.2 mg/d was given only during a 3- month period each year. Then, M 2 g/d continued without L. Food intake was reduced due to lasting satiety. The final check up in February 2021 revealed excellent clinical condition, BM 66.1 kg, BMI

, HbA1c 41 mmol/mol and in

*DOI: http://dx.doi.org/10.5772/intechopen.96237*

39 to 32 kg/m<sup>2</sup>

29.4 kg/m2

.

**5.2 Effects of liraglutide and bariatric surgery**

**5.3 Effects of liraglutide in T2D prevention**

and HbA1c 39 mmol/mol.

*Lady, age 60 y, prediabetes. Evolution of body mass before and with L + M [66] (2011).*

impaired fasting plasma glucose (IFG), BMI 36.4 kg/m2

*Pathophysiologic Approach to Type 2 Diabetes Management: One Centre Experience 1980–2020 DOI: http://dx.doi.org/10.5772/intechopen.96237*

### **5.2 Effects of liraglutide and bariatric surgery**

*Type 2 Diabetes - From Pathophysiology to Cyber Systems*

*Lady, age 57. Therapy and evolution of BMI since the detection of T2D in 2006. M-metformin, S-sitagliptin,* 

*Lady, age 57. Therapy and evolution of HbA1c since the detection of T2D in 2006. M-metformin, S-sitagliptin,* 

*Man, age 57 y, T2D duration 13 y. Evolution of HbA1c with liraglutide and metformin before (2010–2012, blue)* 

**16**

**Figure 19.**

**Figure 17.**

**Figure 18.**

*L-liraglutide (L-start 18.8.2010) [64].*

*and after (2012–2015) bariatric surgery [65] (2015).*

*L-liraglutide (L-start 18.8.2010) [64].*

Our second case report (2010–2016) [65] deals with a temporal positive influence of a 5-year liraglutide therapy on HbA1c (**Figure 19**), BMI and 10-point glyceamic profile in a man with 13-year history of uncontrolled T2D. After one year on liraglutide 1,2 mg/d + metformin 2000–3000 mg/d, the initial decrease of BMI and HbA1c was followed by their slow increase. Following bariatric surgery, the continuing liraglutide and metformin treatment resulted in near-normal HbA1c concentrations not exceeding 51 mmol/mol. The BMI decreased from 39 to 32 kg/m<sup>2</sup> .

#### **5.3 Effects of liraglutide in T2D prevention**

The purpose of this case report (2011) [66] is to demonstrate the effects of 5 month off label administration of L and metformin (M) in a 60y old woman with impaired fasting plasma glucose (IFG), BMI 36.4 kg/m2 , HbA1c 41 mmol/mol and in excellent physical condition. Since 2005 her body mass increased by 10 kg. Recently diagnosed hypertension was successfully treated by metoprolol and losartan (BP 140/80 mmHg, HF 64/min). She was treated by simvastatin since 2008 (LDL cholesterol 3,4 mmol/l). Proinsulin, C-peptide, TSH. T3, T4 and routine laboratory parameters were found within normal limits. Results of SMPG using glucometer Linus, Agamatrix, USA were slightly abnormal. In August 2010 the therapy with L and M started. First evaluation was made in January 2011 (**Figures 20** and **21**). In 2012 – 2014, L 1.2 mg/d was given only during a 3- month period each year. Then, M 2 g/d continued without L. Food intake was reduced due to lasting satiety. The final check up in February 2021 revealed excellent clinical condition, BM 66.1 kg, BMI 29.4 kg/m2 and HbA1c 39 mmol/mol.

**Figure 21.**

*Lady, age 60 y, prediabetes. 10-point PG profile before and with L + M [66] (2011).*

Independently, 4 of other 6 obese persons with IFG/IGT reduced body mass during L supplementation. So, L therapy appears to be a potentially effective approach to prediabetes conditions and its administration should start rather at an early stage.

#### **5.4 Effects of once weekly semaglutide on HbA1c, body mass and well-being**

Effects of long-acting incretin analogs (exenatid QW, dulaglutid [67] and semaglutide [68–77] on metabolism, cardiovascular and renal protection were described in clinical studies REWIND and SUSTAIN 1–10, resp.

Our case report (2019–2020) [78] brings insight on benefits of semaglutide in a 79-year-old lady with long-lasting T2D. She has been suffering from both metformin intolerance and insulinofobia. In the course of a long- lasting period of gliptin therapy, the patient's HbA1c concentration increased to 61 mmol/mol. During the following 4-month period with semaglutide, the patient's mean PG concentration

#### **Figure 22.**

*Lady, age 79 y. Evolution of HbA1c in the course of treatment with saxagliptin, linagliptin and semaglutide, resp., 2018 to 2020 [78].*

**19**

**Figure 24.**

**Figure 23.**

*Pathophysiologic Approach to Type 2 Diabetes Management: One Centre Experience 1980–2020*

of a 10-point daily profile (MPG) decreased from 7.4 mmol/l to 7.0 mmol/l, and her body mass from 80,9 kg to 77,7 kg. One year later, the HbA1c reached 48 mmol/mol (**Figure 22**). No adverse events appeared. We can conclude, the early indication of once-a-week subcutaneously administered semaglutide resulted in improvement of

**5.5 Effects of fixed combination of insulin degludec and incretin liraglutide** 

*Lady, age 77 y, T2D since 1985, cast away syndrome. Evolution of HbA1c in the course of different therapy* 

*Lady, age 77 y, T2D since 1985, cast away syndrome. Evolution of BM in the course of different therapy (MDI-*

Metabolic and cardiovascular benefits of the fixed combination IdegLira were

*DOI: http://dx.doi.org/10.5772/intechopen.96237*

**(IDegLira)**

all investigated parameters of saccharide metabolism.

evaluated in studies DUAL and others. [79–87]

*(MDI-CSII-CSII with iSGLT2-IDegLira only) (1997–2020) [88].*

*CSII-CSII with iSGLT2-IDegLira only) (1995–2020) [88].*

*Pathophysiologic Approach to Type 2 Diabetes Management: One Centre Experience 1980–2020 DOI: http://dx.doi.org/10.5772/intechopen.96237*

of a 10-point daily profile (MPG) decreased from 7.4 mmol/l to 7.0 mmol/l, and her body mass from 80,9 kg to 77,7 kg. One year later, the HbA1c reached 48 mmol/mol (**Figure 22**). No adverse events appeared. We can conclude, the early indication of once-a-week subcutaneously administered semaglutide resulted in improvement of all investigated parameters of saccharide metabolism.
